Department of Biological and Environmental Sciences, Troy University, Troy, Alabama, USA
Received Date: June 20, 2014; Accepted Date: July 15, 2014; Published Date: July 18, 2014
Citation: Chadha T (2014) Bacterial Biofilms: Survival Mechanisms and Antibiotic Resistance. J Bacteriol Parasitol 5:190. doi: 10.4172/2155-9597.1000190
Copyright: © 2014 Chadha T. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Visit for more related articles at Journal of Bacteriology & Parasitology
Biofilm represents single species or multi-species communities that interact and cooperate with each other and their environment to carry out complex processes. One of the most important challenges is to understand intercellular communications that exist within the community that promote biofilm formation. Biofilm currently represents a major health problem as it play an important role in device-related infections such as prosthetic valves, catheters and contact lenses. The present review will focus on the mechanisms that lead to biofilm formation on surfaces and highlight several medically important pathogens.
Biofilm; Extracellular polymeric substances; Antibiotic resistance; Horizontal gene transfer; Nosocomial infections
In nature prokaryotes occupy diverse habitat as they have ability to attach and form communities. Once in a community, bacterial species cooperate, compete and interact with each other and carry out complex processes. Biofilm represents single species of bacteria or multispecies communities. They can be found in nature as well as in industrial and clinical environment. For instance, dental plaque are known to contain as many as 700 species [1-10] growing in Extracellular Polymeric Substances (EPS)
The formation of biofilm begins in stages. In stage one, there is transient binding of planktonic bacteria to a solid surface with characteristic adhesion. In stage two, there is aggregation and formation of micro colonies surrounded by protective secreted molecules known as extra polymeric substance (EPS) matrix. Finally, there is dispersal that involves shedding from the mature biofilm as planktonic bacteria or as micro colonies. This dispersal stage may promote further colonizing the host with biofilms. This may ultimately benefit the organisms due to limited nutrient availability and waste accumulation.
Depending on ecological niche, bacteria are exposed to different stresses such as UV radiation, pH shifts, osmolarity, iron availability, oxygen tension, temperature, nutrient availability and desiccation  that may obstruct their basic activities such as ability to grow and survive. These environment signals trigger the transition from planktonic growth to life on a surface. However, the environmental cues differ greatly among organisms. For instance, Pseudomonas aeruginosa will form biofilms under most conditions that allow growth [11,12]. However, Escherichia coli O157:H7 has been reported to make a biofilm only under low-nutrient conditions. The genetic analysis of biofilm formation by many organisms has revealed that they may utilize multiple genetic pathways to initiate biofilm development . For instance, Vibrio cholera may utilize different pathways for initial attachment depending on the surface to which the organism attaches. For example, the study in vivo has shown that Tcp pilus is required for colonization of the intestine. However, Tcp pilus is not important in attachment to abiotic surfaces. Although, environmental signals may trigger biofilm development, they may vary from organism to organism. In order to gain stability and ecological success, bacterial species has developed adaptive strategies. Thus, bacterial species come together and form biofilm to enhance survival especially under adverse conditions
The major component in the biofilm matrix is water that may measure up to 97% . The secretion of EPS is linked with the genes that are up-regulated in biofilms . The EPS may vary in their composition, chemical and physical properties . The phenotype of mature film depends on the environment in which it develops. The studies have shown that the changes in environment results in phenotypic changes in the biofilm formation [16,18,19]. EPS has also been reported to provide protection from a variety of environmental stresses. For instance, the protective role of EPS was demonstrated as it provided resistance to desiccation in mucoid strains of bacteria such as E. coli when compared to non mucoid variants of the same . The EPS helped bacterial species to adapt to stressful and changeable environmental conditions. The slower growth of bacteria has been observed in biofilm to enhance EPS production for adaptation. The mutants that are unable to synthesize the EPS are usually unable to form biofilms . For instance, E. coli strain that cannot develop normal biofilm is also defective in colonic acid production. The colonic acid is a major EPS synthesized by this organism. . However, in a mixed population, one species producing EPS may provide the stability to mutant type that are unable to synthesize EPS [16,21]
The biofilm enables cells to live close to each other to facilitate exchange of plasmids and free DNA that enable them to overcome different environmental stresses. The bacteria in a biofilm uses chemical communication known as quorum sensing that help them to coordinated their metabolism and other complex processes and adapt to the ongoing changes in the environment. For instance, Bacillus subtilis uses intercellular communication during its metamorphosis into spores to better adapt to changing environmental parameters . The mutant of P. aeruginosa that is unable to synthesize the major quorum-sensing molecules acylhomoserine lactones (acyl-HSLs) was able to produce altered biofilm when compared to its wild type. This demonstrated that these molecules regulate the formation of biofilm structures in this organism. This data strongly suggest that cell-cell communication is essential for this bacterium to establish a well ordered surface community [23,24].
The genetic analysis of Streptococcus gordonii, an oral microbe suggested that cell-to-cell communication may also be important for biofilm development in these gram-positive organisms. The maturation of the biofilm relies on cell-to-cell interactions called co aggregation. The structural and spatial organization can have a profound impact on biofilm ecology. The three dimensional organization of biofilm allow cells to fix their locations with respect to each other  and help in release of distinct environmental signals within a biofilm that provides additional benefits for metabolic cooperation and niches. For instance, cells that are situated near the center of a micro colony are more likely to experience low oxygen tensions. This may provide better environment for strictly anaerobic methanogens that are embedded in EPS 
In nature, microorganisms are exposed to harsh environment such as hydrothermal vents, deep sea vents, acid mine drainage. The physiological adaption to challenging conditions has many benefits. Interestingly, biofilms are involved in the processing of sewage, treatment of groundwater contaminated with petroleum products . The surface-attached biofilms in form trickling filters are used in some waste-water treatment plants. Biofilms are able to accumulate metals and may help in transfer of metals through an ecosystem. For instance, biofilms in acid mine drainage may contribute to the cycling of sulfur 
Biofilms provide an ideal environment for the establishment of syntrophic relationships that enables two metabolically distinct types of bacteria to depend on each other to utilize certain substrates for energy production [27,28]. The study done by Bryant et al. showed that two different organisms interacted syntrophically to convert ethanol to acetate and methane by interspecies hydrogen transfer . These relationships have gained more importance as they may promote pathogenicity of virulent organisms and promote their colonization and survival 
Biofilms are associated with an emergence of antibiotic resistant bacteria. Horizontal gene transfer promotes evolution and genetic diversity of natural microbial communities. The study of gene transfer in natural environments has gained importance by emergence of multidrug-resistant bacteria [5,30-32]. The EPS matrix prevents access of certain antimicrobial agents restricting diffusion of compounds from the surrounding into the biofilm. The classes of antibiotics that are hydrophilic and positively charged, such as aminoglycosides are more obstructed than others.
There may be inactivation of the antibiotics by extracellular polymers or modifying enzymes. The bacteria in a biofilm are 1,000-fold more resistant to antibiotic treatment than the same organism that are grown planktonically [19,33]. The extensive use of antibiotics to promote growth in domestic animals, livestock and agriculture has resulted in selection of antibiotic resistant bacteria [6,34-39]. The prevalence of plasmids in bacteria from diverse habitats and gene transfer by conjugation has resulted in dissemination of genetic information [40,41]. As most of the bacteria in natural settings reside within biofilms, conjugation is one of the most likely mechanisms by which bacteria in biofilms transfer genes within or between populations [42-46]. The study of microcosm dental plaque have shown that Bacillus subtilis strain that harbored a conjugative transposon with tetracycline resistant cassette was able to transfer conjugative transposon to Streptococcus species in biofilm bacteria . These results proved that non oral bacteria have the potential to transfer genes to oral commensals . Clinical biofilm infections have shown that treatment with antibiotics is not a complete solution as symptoms usually recur even after repeated treatments. The antibiotic therapy eliminates the planktonic cells, but the sessile forms are resistant and continue to propagate within the biofilm . However, there is continuous release of antigens and production of antibodies that eventually causes more damage to the surrounding tissue [19,48]
Biofilms play a prominent role in the contamination of medical implants by residing on abiotic surfaces [49,50] such as prosthetic valves, catheters and contact lenses. The bacterial biofilms on prosthetic valves are the leading cause of endocarditis in patients that have undergone heart valve replacement [51,52]. The biofilm formation on urinary catheters is also reported as a leading cause of urinary tract infections [53,54]. Biofilm formation can also occur on contact lenses that may lead to keratitis[55-57].
Biofilm plays a remarkable role in cystic fibrosis (CF) patients that are infected by Pseudomonas aeruginosa. The inherited genetic disorder increases the susceptibility to chronic P. aeruginosa infections although the basis is not yet known. The infection causes hyperactive inflammatory response in the lung that may eventually destroy the functioning of the lung and leads to the death of the patient [12,58,59]. P. aeruginosa species isolated from the CF patients were mucoid with overexpression of EPS called alginate. The aligate may promote biofilm formation and enhance resistance to antibiotics.
Periodontitis is an important case of a biofilm-mediated disease. The main bacterium associated with this disease is Porphyromonas gingivalis  that colonizes in the oral cavity to invade mucosal cells and release toxins. The chronic inflammation may even lead to tooth loss. The bacterium may colonize mucosal and tooth surfaces directly or via interactions with primary colonizers. The primary colonizers are S. gordonii, Streptococcus sanguis, and Streptococcus parasanguis that add up to 60-80% of the early bacterial population [64,65]
The current antibiotic treatment guidelines do not consider the difference in the ecological dynamics that exist between different bacterial species . Antibiotics when administered at concentrations below the minimum inhibitory concentration can induce biofilm formation in a variety of bacterial species [48,67]. This is of major concern as cells that are deep inside the biofilm may be exposed to sub-MIC level of antibiotic. Instead of inhibiting the biofilm, the antibiotic may promote biofilm formation . The other concern is dosing regimen as bacteria are exposed to sub-MIC concentrations of antibiotics at the beginning and end of a dosing regimen . The extensive use and misuse of antibiotics in agriculture, livestock and aquaculture may further exposure of bacteria to low levels of the drugs [5,70,71]
The discovery of surface-attached bacteria happened almost 70 years ago . However, we are still trying to understand the significance of biofilm communities. Interestingly, to understand bacteria as a community takes us away from our traditional view of microbiology. The major challenge is to understand intercellular communications that promote stability in biofilms and usage of models that can mimic natural communities in the laboratory. However, there is some success in this area such as development of model to study catheter- induced bladder infections . The discovery of confocal scanning laser microscopes (CSLM) has further helped to examine the three-dimensional structure and function of biofilms. However, application of modern techniques with the collaborative efforts from scientists from various fields will help to better understand this continuous evolving dynamic world of biofilms
I would like to thank everyone that has helped me in this work. Troy University, Department of Biological & Environmental Sciences